This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The aim of this project is to evaluate the effects of a high-fructose vs. a high-glucose challenge on gene expression (plasma, cerebrospinal fluid and mRNA) of appetite-related hormones in baboons. The recent increase in obesity seems to have paralleled the increase in consumption of foods high in fructose, particularly high-fructose corn syrup. Fructose is associated with body weight gain through its effects on appetite. Fructose raises the blood sugar but does not cause a feeling of fullness in a way that glucose does. Unlike glucose, ingestion of fructose does not cause an increase in leptin and insulin levels (hormones that increase satiety). Similarly it does not suppress ghrelin (a hormone which increases food intake) in the same proportion as glucose. This can cause over consumption of calories and sugar and hence lead to weight gain. Studies in rodents and rhesus macaques have found increased consumption of fructose to be associated with an increase in abdominal adiposity. Using the baboon as our model for study we will expand the investigation of the effects of a high-fructose diet to include its effect at the level of gene expression. Nine baboons (3 fed a high fructose meal, 3 fed a high glucose meal, and 3 control), matched for age and size with no history of gastrointestinal pathologies, inflammation, or diabetes will be utilized. Gene expression (protein and mRNA) of appetite-related hormones will be evaluated. This study will determine the metabolic effects of chronic high-fructose vs. high glucose consumption under well-controlled conditions in the baboon. The preliminary data obtained from this study will be used to establish the baboon as the model for investigating the differential effects of fructose vs. glucose consumption on neuroendocrine factors involved in appetite regulation as part of a larger R01 application now in development.